Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose X-irradiation

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice

Voltage-current and voltage-flux characteristics of asymmetric high TC DC SQUIDs

We report measurements of transfer functions and flux shifts of 20 on-chip high T$_C$ DC SQUIDs half of which were made purposely geometrically asymmetric. All of these SQUIDs were fabricated using standard high T$_C$ thin film technology and they were single layer ones, having 140 nm thickness of YBa$_2$Cu$_3$O$_{7-x}$ film deposited by laser ablation onto MgO bicrystal substrates with 24$^0$ misorientation angle. For every SQUID the parameters of its intrinsic asymmetry, i. e., the density of critical current and resistivity of every junction, were measured directly and independently. We showed that the main reason for the on-chip spreading of SQUIDs' voltage-current and voltage-flux characteristics was the intrinsic asymmetry. We found that for SQUIDs with a relative large inductance ($L>120$ pH) both the voltage modulation and the transfer function were not very sensitive to the junctions asymmetry, whereas SQUIDs with smaller inductance ($L\simeq 65-75$ pH) were more sensitive. The results obtained in the paper are important for the implementation in the sensitive instruments based on high T$_C$ SQUID arrays and gratings.Comment: 11 pages, 4 tables, 17 figures This version is substantially modified. The Introduction and Section 2 are completely rewritten, while experimental part is mainly the same as in previous versio

Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction

Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853(∗)]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage

Mineralogical and geochemical characterization of high-medieval lead–silver smelting slags from Wiesloch near Heidelberg (Germany)—an approach to process reconstruction

Here, we present detailed electron microprobe analyses and age data of high-medieval lead–silver smelting slags. The mineral composition data provide a database of all silicate and oxide phases in the slag. Bulk chemistry as well as mineral composition is used to reconstruct liquidus, solidus, and viscosity of the slag melt. By calculating the mass balance of the smelting process, a mass ratio of the various compounds used in the smelting process is determined. Through this we were able to discriminate qualitatively between non-ferrous metal smelting slags and bloomery slags. We also report a new type and process of silver production in which argentiferous galmei (zinc carbonate) was used as a main silver ore together with galena. The results indicate a sophisticated high-medieval smelting technology, in which a slag with a low liquidus and a low viscosity was created

Formation of the Wiesloch Mississippi Valley-type Zn-Pb-Ag deposit in the extensional setting of the Upper Rhinegraben, SW Germany

The Mississippi Valley-type (MVT) Zn-Pb-Ag deposit in the Wiesloch area, Southwest Germany, is controlled by graben-related faults of the Upper Rhinegraben. Mineralization occurs as vein fillings and irregular replacement ore bodies consisting of sphalerite, banded sphalerite, galena, pyrite, sulfosalts (jordanite and geocronite), barite, and calcite in the Middle Triassic carbonate host rock. Combining paragenetic information, fluid inclusion investigations, stable isotope and mineral chemistry with thermodynamic modeling, we have derived a model for the formation of the Wiesloch deposit. This model involves fluid mixing between ascending hot brines (originating in the crystalline basement) with sedimentary formation waters. The ascending brines originally had a near-neutral pH (around 6) and intermediate oxidation state, reflecting equilibrium with granites and gneisses in the basement. During fluid ascent and cooling, the pH of the brine shifted towards more acidic (around 4) and the oxidation state increased to conditions above the hematite-magnetite buffer. These chemical characteristics contrast strongly with those of the pore and fracture fluid residing in the limestone aquifer, which had a pH between 8 and 9 in equilibrium with calcite and was rather reduced due to the presence of organic matter in the limestone. Mixing between these two fluids resulted in a strong decrease in the solubility of silver-bearing sphalerite and galena, and calcite. Besides Wiesloch, several Pb-Zn deposits are known along the Upper Rhinegraben, including hydrothermal vein-type deposits like Badenweiler and the Michael mine near Lahr. They all share the same fluid origin and formation process and only differ in details of their host rock and fluid cooling paths. The mechanism of fluid mixing also seems to be responsible for the formation of other MVT deposits in Europe (e. g., Réocin, Northern Spain; Trèves, Southern France; and Cracow-Silesia, Poland), which show notable similarities in terms of their age, mineralogy. and mineral chemistry to the MVT deposit near Wiesloch.20 page(s